Medicinal Properties of Substances Occurring in Higher Basidiomycetes Mushrooms: Current Perspectives
International Journal of Medicinal Mushrooms, Vol 1, 47-50, (1999) Solomon P. Wasser, Alexander L. Weis International Center for Cryptogamic Plants and Fungi, Institute of Evolution, University of Haifa, Israel International Myko Biologics, Inc., San Antonio, TX, USA M.G. Kholodny Institute of Botany, National Academy of Sciences of Ukraine, Kiev, Ukraine CARDIOVASCULAR AND HYPERCHOLESTEROLEMIA EFFECTS The major cause of death in the Western countries is coronary artery disease. A primary risk
factor is hypercholesterolelmia, which contributes to hardening of the arteries. In humans,
50% or more of the total cholesterol is derived from de novo synthesis (Rosenfeld, 1989;
Steinberg et al., 1989). Clinical intervention studies have demonstrated the therapeutic
importance of correcting the hypercholesterolemia. The initial step in lowering cholesterol is
a special diet low in fat and saturated fatty acids and rich in crude fibers.
Drug therapy is the next step. The best-known pharmacologic agent that was approved in
1987 is lovastatin (mevinolin) and its analogues (Endo, 1988). This low molecular weight
substance is the competitive inhibitor of HMG Co A reductase, the key enzyme in cholesterol
metabolism that catalyzes the reduction of HMG CoA into mevalonate.
The best known organisms for potential producers of lovastatin from edible higher
Basidiomycetes mushrooms are species of the genus Pleurotus (Gunde-Cimerman et al;.,
1993a,b; Gunde-Cimerman and Cimerman, 1995). The presences of the inhibitor was
determined in four species: P. ostreatus, P. cornucopiae, P. eryngii, and P. sapidus. The
highest content of lovastatin was found in the fruiting bodies of the P. ostreatus. The
appearance of the inhibitor during the development of the fruiting bodies was found in the
vegetative mycelium, in the primordial, and in different parts of fruiting bodies of different
sizes; less lovastatin was found in stipes when compared with pileus (fig. 5) or in nature
stages in the lamellae and basidioiospores (Gund-Cimerman and Cimerman, 1995)
It was shown that lovastatin at the beginning of mushroom growth is unfortunately
distributed in small fruit bodies, and there are no substantial differences between the pileus
and the stipe. During fruit body growth, the majority of lovastatin is first transferred to the
pileus and later the lamellae. Mature fruiting bodies have a diameter of approximately 15 cm
and disperse large amounts of basidiospores. These contain less lovastatin in the lamellae
when compared with the smaller, 10 cm diameter; less mature mushrooms this transfer is still
incomplete (Gunde-Cimerman and cimerman, 1995).
In a series of experiments conducted by Bobek et al. (1991a,b, 1993), it has been found that
the addition of 2% to 4% of P. ostreatus to the hyperlipidemic diet efficiently prevented
accumulation of C and triacly-glycerols in both sera and livers of animals with exogenous,
endogenous, or genetically induced hyperlipidemia. VLDL cholesterol had the dominant
role in the reduction of serum C up to 80% induced by the whole mushroom pr its water and
30% of ethanol extracts. The authors attributed this effect to the fiber pulp complex of the
oyster mushroom, which limits the resorption of C and gastrointestinal tract, and to an
undefined substance which influences, as well, metabolisms outside the phase of resorption.
(Bobek et al., 1991a,b, 1993). Ryong et al. (1989) have tested alcohol and water extracts of
20 different edible mushrooms in tissue primary culture of cells isolated from atherosclerotic
action. Four mushrooms also decreased atherogenic effects by 20% to 40% in sera collected
from coronary heart disease patients. In these experiments the effect of dietary fibers was
excluded and the efficiency was attributed to an unknown active component (Ryong et al.,
1989). Authors suggest that this unknown substance is lovastatin, which can be found in
high quantities in the fruiting bodies of various cultured Pleurotus species. Therefore,
mature fruiting bodies of P. ostreatus could be recommended for consumption as a natural
cholesterol-lowering agent. Lovastatin appears early in the life cycle of the mushroom, in the
mycelia from which primordial are being formed.
It is known that Lentinus edodes is able to lower BSC via a factor known as eritadenine (also
known as “Lentinacin” or “Lentysine”) was isolated from an 80% ethanol extract of Shiitake
mushroom fruiting bodies by absorption on a Amberlite IR-120 (H+) column, followed by
elution with 4% NH 4 OH (chibata et al., 1969). A crystalline product had the following
properties: mp 261-263° C, C9H11O4N5, MW 253, \ 261 .5 nm (E=14,508)m, Nasapt mp 266
–268 C (decomposition), {a} D + 45.5 (C=1, H2O). Hydrolyses in 6N HCI at 110 C for 72h
yielded glycine and new amino acid. Eritadenine apparently reduces serum cholesterol in
mice. Its action is not inhibition of cholesterol biosynthesis, but rather the acceleration of
excretion of ingested cholesterol and its metabolic decompositions (Makita et al., 1972, cited
Apparently, Eritadenine reduces BSC in mice, not by the inhibition of cholesterol
biosynthesis but by the acceleration of the excretion of ingested cholesterol and its metabolic
decomposition (S. Suzuki and Oshima, 1974, 1976; Higushi et al., 1978; Yagishita et al.,
1977, 1978). Eritadenine has been shown to lower blood levels of cholesterol and lipids in
animals (Yamamura and Cochran, 1976) Added to the diet of rats, Eritadenine (0.005%)
caused a 25% decrease in total cholesterol in as little as one week (Chibata et al., 1969) The
cholesterol-lowering activity of this substance is more pronounced in rats fed a high fat diet
than those on a low-fat diet (Rokujo et al., 1969). Although feeding studies with humans
have indicated a similar effect, further systematic research is needed. S. Suzuki and Ohshima
(1974, 1976) have shown that dietary shiitake mushroom lowered BSC levels. Various
studies have confirmed (Kimoto et al., 1976;m Kabir and Kmura, 1989) that shiitake
mushroom can lower both blood pressure and free cholesterol in plasma, as well as accelerate
accumulation of lipids in the liver, by removing them from circulation.
Nucleic acid compound in L. edodes extract have been shown a strong platelet agglutination
inhibitive effect (antithrombotic activity). An extract of L. edodes with antithrombotic
activity was studied by high-performance liquid chromatography (HPLC). ATP, ADP,
UDPG, 5’-GMP, 5’UMP, 5’-CMP, 5’-AMP, uridine, eritadenine, and deoxylentinacin were
identified. More antithrombotic activity was shown by 5’-AMP, 5’GMP, eritadenine, and
deoxylentinacin (Hokama and Hokama, 1981; Kabir and Kimura, 1989).
Auriculari auricula-judae has shown the following effects and activities in studies on mice
and rats: anticoagulation, lowered total cholesterol, triglyceride, and lipid levels (Chen, 1989;
Sheng and Chen, 1990); and antiaggregatory activity on blood platelets, which might make it
beneficial for coronary heart disease (Agarwal et al., 1982). This mushroom is traditionally
Tremella fuciformis polysaccharides and spore extracts have demonstrated antilipemic
activity. T. fuciformis lowered the LDL- cholesterol in rats fed the preparation, which also
contained butter sugar, and egg yolks, by 30% over controls (Nakajima, et al., 1989). T. fuciformis polysaccharides prolonged thrombus formation, reduced thrombus size, reduced
blood platelet adherence, blood viscosity, and positively influenced other blood coagulation
parameters of survival in mice (Sheng and Chen, 1990).
Animal studies on Armillriella mellea demonstrated that it decreases heart rate, reduces
peripheral and coronary vascular resistance, and increases cerebral blood flow (Chang and
But, 1986). AMG-1-a compound isolated from this mushroom exhibits a cerebral-protective
effect (Watanabe et al., 1990), and increases coronary oxygen efficiency without altering
Grifola frondosa reduced blood pressure in rats without changing plasma HDL levels (Kyoto
et al., 1988). Adachi and coworkers (1988) found a blood pressure lowering effect with the
powder of G. frondosa fed to hypertensive rats in their normal food. The effect was of rapid
onset, short lived and dose dependent. An aqueous extract of G. frondosa also reduced
serum cholesterol levels in rats (Mizuno, 1977).
A glycoprotein obtained from submerged cultured mycelial biomass of Trametes sp. showed
activity (in animal and in vitro test). Against experimental hypertension and thrombosis.
The protein inhibits blood platelet aggregation and is antihyperlipemic and antiarrhythmic.
(Ikuzawa, 1985) Trametes versicolor has been shown to lower serum chooesterol in animals
(Yagishita et al., 1977). PKS ( beta-glucan protein) from T. versicolor has been used in
clinical studies. Tsukagoshi et al (1984) have reported that PSK causes a significant decrease
in LDL cholesterol in hyperlipidemia (stage 11a ) patients.
The Volvariella volvacea cardioactive proteins are know to lower blood pressure (Cochran,